Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer

Sun, Yanming; Yao, Zhitao; Zhao, Zhihua; Xiao, Haifeng; Xia, Mengna; Jiang, Xin; Sun, Chuntao

doi:10.3892/etm.2018.6342

Cited by 20 publications

(25 citation statements)

References 42 publications

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“…Upon unraveling the epidemiologic association between NK cells and cancer [24], research efforts ensued to use NK cells in the treatment of cancer via adoptive cellular transfer. In both in vitro and in vivo studies, NK cells have been shown to mediate direct killing of human cancer cells in acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, glioblastoma, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, melanoma, and carcinomas of the breast, lung, ovary, colon, pancreas, renal cells, and stomach [17,30,31,32,33,34,35,36].…”

Section: Low Nk Cell Activity and Cancer Developmentmentioning

confidence: 99%

“…Early trials have been conducted in advanced cancer patients with a high tumor burden. In those studies, signs of clinical response were observed as was indicated by preclinical models that NK cell therapy prevented migration and invasion of cancer cells contributing to prevention of systemic metastasis [36]. However, such response was not dramatic as it did not meet the expectation of the scientific community.…”

Section: Strategies To Enhance the Effect Of Nk Cell Therapymentioning

confidence: 99%

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Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

Lee

Kwack

et al. 2019

Cancers

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In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. In this regard, the autologous NK cell therapy is safer. This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. A recent study discovered that NK cell specific genetic defects are closely associated with the tumor immune microenvironment that determines clinical outcomes. This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors.

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Section: Low Nk Cell Activity and Cancer Developmentmentioning

confidence: 99%

Section: Strategies To Enhance the Effect Of Nk Cell Therapymentioning

confidence: 99%

Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

Lee

Kwack

et al. 2019

Cancers

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“…In preceding studies, the antitumour effects were reported by injecting 10 6 NK cells twice or single injection of 10 7 cells to a mouse. 32 , 33 No toxic effects were mentioned in both reports, suggesting that NK cells of 2 × 10 6 –10 7 cells per mouse can exert antitumour effects without toxic phenotypes. In addition, we observed no apparent tumour formation in 15 weeks after the last injection of the treated NK cells (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 87%

Development of a protein-based system for transient epigenetic repression of immune checkpoint molecule and enhancement of antitumour activity of natural killer cells

et al. 2020

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Background Immune checkpoint blockade (ICB) therapy improved the prognosis of cancer patients, but general administration of ICBs occasionally induces side effects that include immune-related adverse events and tumour hyper-progression. Here, we established a protein-based system, by which endogenous expression of IC molecule in natural killer (NK) cells was transiently repressed on enhancement of their antitumour activity. Methods A protein-based genome modulator (GM) system is composed of a transcription activator-like effector (TALE), DNA methyltransferase and a newly identified potent cell-penetrating peptide with nuclear-trafficking property named NTP. TALE was designed to target the promoter region of the programmed cell death-1 ( PD-1 ) gene. After culturing human NK cells in the presence of NTP-GM protein, we examined endogenous PD-1 expression and antitumour activity of the treated cells. Results NTP-GM protein efficiently downregulated PD-1 expression in NK cells with increased CpG DNA methylation in the promoter region. The antitumour activity of the treated NK cells was enhanced, and repeated intraperitoneal administrations of the treated NK cells attenuated tumour growth of programmed death-ligand 1-positive tumour cells in vivo. Conclusions Because the incorporated NTP-GM protein was quickly degraded and negligible in the administered NK cells, the NTP-GM system could be an alternative option of an ICB without side effects.

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“…Several studies have shown the following effects of NK cells in different cancers: NK cells have been shown to be effective in patients with advanced lung cancer; Herceptintreated NK cells have been found to have therapeutic potential in the treatment of patients with human epidermal growth factor receptor 2 (Her2 + ) and Herceptin-intolerant breast cancer; expanded and cryopreserved NK cells are promising candidates for cellular immunotherapy in patients with pancreatic carcinoma; NK cells inhibit metastesis of ovarian carcinoma cells in murine models; CIK cells may become a novel therapeutic modality for rhabdomyosarcoma after allogeneic HSCT; CAR-engineered CIK cells may become valuable in the treatment of HR soft tissue sarcoma in children; and expanded and CIK cells are safe and well tolerated and they enhance cytotoxicity against gastric carcinoma [162,[265][266][267][268][269][270][271]. A meta-analysis, that included 29 clinical trials involving 2610 patients, has been shown that the combination of CIK/DC-CIK immunotherapy and cytotoxic chemotherapy: enhances the immune function of patients, alleviates the adverse effects of chemotherapy, and improves the overall response, disease control, and quality of life [272].…”

Section: Nk Cells In Solid Tumorsmentioning

confidence: 99%